POS0566 PREDICTORS OF RESPONSE TO METHOTREXATE MONOTHERAPY IN ACTIVE RHEUMATOID ARTHRITIS: RESULTS FROM A MULTICENTRE, RANDOMIZED CONTROLLED TRIAL (MEIRA)
Authors: S. Jain, V. Dhir, A. Aggarwal, R. Gupta, B. Leishangthem, G. Naidu, A. Khullar, V. Dhawan, S. K. Sharma, A. Sharma, S. Jain
Journal: Annals of the Rheumatic Diseases (2022)

Background Methotrexate (MTX) is the gold standard, first-line therapy for rheumatoid arthritis (RA). However, not all patients respond to MTX, and the predictors of its response or non-response have not yet been reliably identified. Identification of these predictors will facilitate personalized therapeutic choices, and improve patient outcomes. Objectives To identify the clinico-laboratory predictors of response to MTX monotherapy in active RA. Methods This study included patients with active RA (SJC≥2 and TJC≥4) aged 18-55 years, with disease duration &lt;5 years, who were not receiving DMARDs (except HCQ and low-dose prednisolone) and had been enrolled in the multicentre, parallel group RCT comparing two different MTX escalation strategies in RA (MEIRA) 1 . All these patients received MTX monotherapy which was started at 15 mg/week, escalated to 25 mg/week by 4-8 weeks, and continued till 16 weeks. MTX response was defined as EULAR good or moderate response (based on DAS28-CRP-3v) at 16 weeks. Stepwise, multivariable logistic regression was done using key demographic (age, gender, BMI, comorbidities), clinical (disease duration, DAS28, HAQ), and laboratory parameters (RF, anti-CCP, ESR, CRP, RBC MTX-polyglutamates 1-4, IL-6, MMP-3) as independent variables to identify predictors of MTX response. A two-tailed p-value &lt;0.05 was used for defining statistical significance. (Trial Reg: CTRI/2018/12/016549) Results Out of a total of 178 included patients [84% females, mean age 40 (9) years, mean DAS28-CRP=5.4 (1.1)], 113 (63.5%) were classified as MTX responders at 16 weeks. Age (OR=0.95, p=0.01), BMI (OR=1.12, p=0.006), and RF (OR=0.34, p=0.045) were found to be independent predictors of MTX response on multivariable analysis (Table 1). On sensitivity analysis with DAS28-ESR-based EULAR response, age (OR=0.94, p=0.003) and RF (OR=0.42, p=0.059) were replicated as independent predictors of MTX response, in addition to pre-treatment swollen joint count (OR=0.94, p=0.05). Table 1. Results of multivariable logistic regression analysis for prediction of response (as defined by DAS28-CRP-based EULAR good or moderate response) to methotrexate monotherapy in RA Variable OR (unadjusted) Unadjusted p-value OR (adjusted) Adjusted p-value Age 0.97 (0.93-1.002) 0.06 0.95 (0.91-0.99) 0.01 Male sex 0.78 (0.35-1.76) 0.55 - BMI 1.1 (1.02-1.19) 0.01 1.12 (1.03-1.22) 0.006 Presence of comorbidities 0.67 (0.31-1.44) 0.31 - Disease duration 0.98 (0.79-1.22) 0.87 - Baseline DAS28 1.1 (0.81-1.49) 0.54 - Baseline HAQ 1.04 (0.66-1.64) 0.86 - Baseline TJC 1.01 (0.96-1.05) 0.72 - Baseline SJC 0.97 (0.91-1.02) 0.24 - Baseline ESR 1.01 (1.00-1.02) 0.27 - Baseline CRP 1.00 (0.99-1.01) 0.85 - RF positive 0.31 (0.11-0.85) 0.02 0.34 (0.12-0.98) 0.045 Anti-CCP positive 0.73 (0.27-1.99) 0.54 - MTX PG1 (16 weeks) 0.99 (0.94-1.04) 0.69 - MTX PG2 (16 weeks) 0.98 (0.95-1.02) 0.37 - MTX PG3 (16 weeks) 0.99 (0.96-1.02) 0.43 - MTX PG4 (16 weeks) 0.99 (0.95-1.03) 0.62 - Serum IL-6 (baseline) 0.98 (0.95-1.02) 0.33 - Serum MMP-3 (baseline) 1.00 (1.00-1.00) 0.48 - BMI= Body Mass Index, CCP= Cyclic Citrullinated Peptides, CRP= C-reactive protein, DAS= Disease Activity Score, ESR= Erythrocyte Sedimentation Rate, HAQ= Health Assessment Questionnaire, MTX= Methotrexate, PG= polyglutamate, OR=Odds Ratio, RF=Rheumatoid Factor, SJC= Swollen Joint Count, TJC= Tender Joint Count Note: Only variables with p-value &lt;0.2 on univariable analysis were included in the multivariable analysis. Conclusion Younger age, RF negativity, higher BMI, and lower pre-treatment swollen joint count are potential predictors of response to MTX monotherapy in RA. References [1]Jain S, Dhir V, Aggarwal A, et al. Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthritis: a multicentre, parallel group, randomised controlled trial. Ann Rheum Dis. 2021;80(11):1376-1384. Disclosure of Interests None declared.